12-Lipoxygenase in Opioid-Induced Delayed Cardioprotection: Gene Array, Mass Spectrometric, and Pharmacological Analyses

• Published in: Circulation research 2003-04, Vol.92 (6), p.676-682
• Main Authors: Patel, Hemal H, Fryer, Ryan M, Gross, Eric R, Bundey, Richard A, Hsu, Anna K, Isbell, Marilyn, Eusebi, Leonard O.V, Jensen, Roderick V, Gullans, Steven R, Insel, Paul A, Nithipatikom, Kasem, Gross, Garrett J
• Format: Article
• Language: English
• Subjects: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - biosynthesis; Animals; Arachidonate 12-Lipoxygenase - genetics; Arachidonate 12-Lipoxygenase - physiology; Arachidonic Acid - metabolism; Benzamides - pharmacology; Biological and medical sciences; Blotting, Western; Cardiotonic Agents - pharmacology; Cardiovascular system; Enzyme Inhibitors - pharmacology; Gene Expression Profiling; Hemodynamics - drug effects; Ischemic Preconditioning, Myocardial; Kinetics; Lipoxygenase Inhibitors; Male; Medical sciences; Miscellaneous; Myocardial Reperfusion Injury - enzymology; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - prevention & control; Myocardium - enzymology; Oligonucleotide Array Sequence Analysis; Pharmacology. Drug treatments; Piperazines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta - agonists; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Spectrometry, Mass, Electrospray Ionization
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.0000065167.52922.F6

ABSTRACT—12-Lipoxygenase (12-LO) has been shown to be a factor in acute ischemic preconditioning (IPC) in the isolated rat heart; however, no studies have been reported in delayed PC. We characterized the role of 12-LO in an intact rat model of delayed PC induced by a δ-opioid agonist SNC-121 (SNC). Rats were pretreated with SNC and allowed to recover for 24 hours. They were then treated with either baicalein or phenidone, 2 selective 12-LO inhibitors. In addition, SNC-pretreated rats had plasma samples isolated at different times after ischemia-reperfusion for liquid chromatographic–mass spectrometric analysis of the major metabolic product of 12-LO, 12-HETE. Similar studies were conducted with inhibitors. Gene array data showed a significant induction of 12-LO message (P